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pH-Sensitive Nanoformulated Triptolide as a Targeted Therapeutic Strategy for Hepatocellular Carcinoma

Cited 95 time in Web of Science Cited 96 time in Scopus
Issue Date
2014-08
Citation
ACS Nano, Vol.8 No.8, pp.8027-8039
Keywords
hepatocellular carcinomatriptolidepH sensitive polymertargeted cancer therapydrug delivery
Abstract
Hepatocellular carcinoma (HCC) has one of the worst prognoses for survival as it is poorly responsive to both conventional chemotherapy and mechanism-directed therapy. This results from a lack of therapeutic concentration in the tumor tissue coupled with the highly toxic off-site effects exhibited by these compounds. Consequently, we believe the best packaging for holistic therapy for HCC will involve three components: a potent therapeutic a rationally designed drug delivery vehicle to enrich the target site concentration of the drug, and a surfaceligand that can enable a greater propensity to internalization by tumor cells compared to the parenchyma. We screened a library containing hundreds of compounds against a panel of HCC cells and found the natural product triptolide, to be more effective than sorafenib, doxorubicin, and daunorubicin, which are the current standards of therapy. However, the potential clinical application of triptolide is limited due to its poor solubility and high toxicity. Consequently, we synthesized tumor pH sensitive nanoformulated triptolide coated with folate for use in an HCC-subpopulation that overexpresses the folate receptor. Our results show triptolide itself can prevent disease progression, but at the cost of significant toxicity. Conversely, our pH-sensitive nanoformulated triptolide facilitates uptake into the tumor, and specifically
ISSN
1936-0851
URI
https://hdl.handle.net/10371/166108
DOI
https://doi.org/10.1021/nn502074x
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College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Journal Papers (저널논문_화학생물공학부)
College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Chemical Convergence for Energy and Environment (에너지환경 화학융합기술전공)Journal Papers (저널논문_에너지환경 화학융합기술전공)
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